EFFECT OF PHOSPHORYLATION ON TETRAMERIZATION OF THE TUMOR SUPPRESSOR PROTEIN P53

摘要: Human tumor suppressor protein p53 is a 393-amino acid phosphoprotein that enhances transcription in response to DNA damage from several genes regulate cell cycle progression. The tetrameric state of critical wild-type function; the tetramerization element located C-terminal region protein. This phosphorylated at evolutionarily conserved serines, suggesting phosphorylation may be an important regulator function. In order determine effect on tetramer formation, we synthesized phosphopeptides corresponding p53(Ser303–Asp393) with phosphate incorporated Ser315, Ser378, or Ser392, and both Ser315 Ser392. Equilibrium ultracentrifugation analysis showed Ser392 increased association constant for formation nearly ten-fold. By itself, Ser378 had little but largely reversed Analysis by calorimetry suggests influence subunit affinity enthalpy driven process.